Smooth Muscle Proliferation in Chronically Injured Canine Pulmonary Arteries Is Reduced by a Potent Platelet Aggregation Inhibitor U-53,059

Robert G Schaub; James C Keith Jr; Carol A Simmons; Clarence A Rawlings

doi:10.1055/s-0038-1661313

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1985; 53(03): 351-355
DOI: 10.1055/s-0038-1661313

Original Article

Schattauer GmbH Stuttgart

Smooth Muscle Proliferation in Chronically Injured Canine Pulmonary Arteries Is Reduced by a Potent Platelet Aggregation Inhibitor U-53,059

Authors

Robert G Schaub

¹The Department of Atherosclerosis and Thrombosis Research, The Upjohn Company, Kalamazoo, MI, USA
James C Keith Jr

²The Department of Veterinary Biology, Virginia Polytechnical Institute, Blacksburg, VA, USA
Carol A Simmons

¹The Department of Atherosclerosis and Thrombosis Research, The Upjohn Company, Kalamazoo, MI, USA
Clarence A Rawlings

³The Department of Small Animal Medicine, The University of Georgia, Athens, GA, USA

Abstract

als PDF herunterladen

Summary

Dirofilaria immitis (DI) infection chronically injures canine pulmonary arteries. This injury produces endothelial cell loss, platelet/leukocyte adhesion, and smooth muscle proliferation. In the present study we assessed the effect of the cyclooxygenase inhibitor, U-53,059, on platelet function, platelet kinetics, coagulation, and smooth muscle proliferation in DI infected dogs.

Platelet aggregation to the combination of arachidonic acid/ ADP was significantly inhibited by U-53,059. Coagulation and hematologic parameters were not effected by either DI infection or U-53,059 treatment. Platelet survival and the number of platelet dense granules were reduced in DI infection. Quantification of the lesions demonstrated that U-53,059 reduced both severity and density compared to non-treated dogs. U-53,059 is a potent and effective inhibitor of platelet aggregation which modifies smooth muscle proliferation produced by chronic vascular injury.

Keywords

Platelets - Myointimal proliferation - Vascular injury

PDF (286 kb)

Referenzen

References
1 Schaub RG, Simmons CA. Medial smooth muscle proliferation in the balloon injured rabbit aorta: Effect of thiazole compound with platelet inhibitory activity. Thromb Haemostas 1984; 51: 75-78
2 Schaub RG, Keith Jr JC, Rawlings CA. Myointimal proliferation in canine pulmonary arteries. Am J Pathol 1981; 103: 440-449
3 Schaub RG, Keith Jr JC, Rawlings CA. The effect of acetylsalicylate acid on vascular damage and myointimal proliferation in canine arteries subjected to chronic injury by Dirofiliaria immitis. Am J Vet Res 1983; 44: 449-454
4 Sharefkin J, Rich NM. Technical consideration in the study of ¹¹¹Indium oxine labelled platelet survival patterns in dogs. Lab Anim Sci 1982; 32: 183-186
5 Wilkinson AR, Hawker RJ, Hawker LM. ¹¹¹Indium labelled canine platelets. Thromb Res 1978; 13: 175-182
6 Schaub RG, Rawlings CA, Stewart GJ. Scanning electron microscopy of canine pulmonary arteries and veins. Am J Vet Res 1980; 41: 1441-1446
7 Madewell BR, Feldman BF, O’Neill S. Coagulation abnormalities in dogs with neoplastic disease. Thromb Haemostas 1980; 44: 35-38
8 Niewiarowski S, Gurewich V. Laboratory identification of intravascular coagulation. J Lab Clin Med 1971; 77: 665-676
9 Fry D. Acute vascular endothelial changes associated with increase blood velocity gradients. Cir Res 1968; 22: 165-197
10 Motomiya M, Karino T. Flow patterns in the human carotid artery bifurcation. Stroke 1984; 15: 50-56
11 Cornhill JF, Roach MR. A quantitative study of the localization of atherosclerotic lesions in the rabbit aorta. Atherosclerosis 1976; 23: 489-501
12 Lutz RJ, Cannon JN, Bischoff KB, Dedrick RL, Stiles RK, Fry DL. Wall shear stress distribution in a model canine artery during steady flow. Cir Res 1977; 41: 391-399
13 Nishizawa EE, Mendoza AR, Honohan T, Annis KA. A thiazole compound with potential anti-thrombotic activity. Thromb Haemostas 1982; 47: 173-176
14 Linet O, Eckert S, Gruber C, Huang D. The effects of an oral antiplatelet agent, U-53,059 in man. Circulation 1982; 66: 11-323
15 Harker LA, Harlan JM, Ross R. Effect of sulfinpyrazone on homocysteine-induced endothelial injury and arteriosclerosis in baboons. Circ Res 1983; 53: 731-739
16 Winocour PD, Kinlough-Rathbone RL, Richardson M, Mustard JF. Reversal of shortened platelet survival in rats by the antifibrinolytic agent epsilon aminocaproic acid. J Clin Invest 1983; 71: 159-164
17 Steele P, Battock D, Genton E. Effects of clofibrate and sulfinpyrazone on platelet survival in coronary artery disease. Circulation 1975; 52: 473-476
18 Barrett PA, Butler KD. Shortening of platelet survival by induced hypercholesterolemia in rabbits and its prolongation by Anagrelide. Thromb Haemostas 1983; 50: 656-659
19 Davis RG, White JG. Localization of 5-hydroxytryptamine in blood platelets. A radioautographic an ultrastructural study Br J Haematol 1968; 15: 93-99
20 Martin JH, Carson FL, Race GJ. Calcium containing platelet granules. J Cell Biol 1974; 60: 775-777
21 White JG, Gerrard JM. Ultrastructural features of abnormal blood platelets. Am J Pathol 1976; 83: 590-632
22 Schaub RG, Rawlings CA. Pulmonary vascular response during various phases of canine heartworm disease: A scanning electron microscopic study. Am J Vet Res 1980; 41: 1082-1089
23 Rawlings CA, Schaub RG, Keith Jr JC. Aspirin reduces pulmonary arteriosclerosis produced by chronic vascular injury. Fed Proc 1984; 43: 976
24 Schaub RG, Rawlings CA, Keith Jr JC. Effect of long-term aspirin treatment of platelet adhesion to chronically damaged canine pulmonary arteries. Thromb Haemostas 1981; 46: 680-683